In a variety of fields including the field of clinical laboratory test, immunological measurement methods utilizing antigen-antibody reactions are widely used as a method for quantitatively determining a trace test substance contained in a measurement sample. Especially, latex immunoturbidimetric method using latex particles as a carrier for an antigen or an antibody is simply operated and takes a short period of time for the measurement. Therefore, the number of kinds of trace test substances to be measured by employing the latex immunoturbidimetric method as a measuring method is further increasing.
For quantitatively determining a test substance of an antigen, an antibody or the like contained in a measurement sample by the latex immunoturbidimetric method, change in absorbance caused by aggregation of latex particles carrying the antigen or the antibody (hereinafter sometimes referred to as “coated latex particles”) is optically detected. This change in absorbance is on the basis of change in apparent particle sizes of aggregates formed by the aggregation of the coated latex particles.
As the latex particles used as a carrier in the latex immunoturbidimetric method, polystyrene latex particles containing polystyrene as a principal component have been conventionally used because antigen- or antibody-coating (immobilization) is easy, they are comparatively inexpensive and they can be easily controlled in the polymerization reaction (Patent Literature 1 and the like). In the case where polystyrene latex particles are used as a carrier in the latex immunoturbidimetric method, however, if the concentration of a test substance in a measurement sample is dilute, then the number of aggregates to be formed is small, and the apparent particle sizes of the aggregates are also small as compared with the case where the concentration of the test substance relative to the number of latex particles falls within an appropriate range, resulting in a disadvantageously insufficient sensitivity.
Accordingly, in order to improve the measurement sensitivity that is lowered when the concentration of a test substance is dilute, an attempt has been made to increase the particle size of the polystyrene latex particles so as to increase the apparent particle size of aggregates to be formed.
When the particle size of the latex particles is too large, however, it is necessary to make adjustment by decreasing the concentration of coated latex particles in a reaction solution to be applicable to an optical measuring device to be used, because of the upper limit of the absorbance measurable by the optical measuring device. Lowering the concentration of coated latex particles in a reaction solution reduced the probability of the coated latex particles encountering with the test substance within a certain period of time, and measurements without the expected improvement in the sensitivity were often experienced. Moreover, when the particle size of the latex particles working as a carrier is increased, the latex particles are liable to precipitate, and hence, if a measurement reagent containing the coated latex particles is stored in the form of a solution, the storage stability is degraded.
In this manner, when the method in which the particle size of the polystyrene latex particles is increased is employed, although the improvement in the measurement sensitivity can be expected up to a given particle size, if the particle size is increased beyond the given size, there arise problems in which the measurement sensitivity is degraded on the contrary and the storage stability of the measurement reagent is degraded.
As a countermeasure, Patent Literature 2 discloses a method for improving the measurement sensitivity by increasing the refractive index of latex particles without increasing the particle size thereof. Even when the latex particles described in Patent Literature 2 are used, however, there still arises a problem in which expected measurement sensitivity cannot be actually attained.